Currently, diagnoses of AIP are carried out based on “Autoimmune pancreatitis diagnostic criteria” released by Japan Pancreas Society in 2002. According to the criteria, a sufficient condition for the diagnosis is that any one of hypergammaglobulinemia, hyperimmunoglobulinemia G, and autoantibodies, all of which are items in a blood test, is observed. Further, it has been reported that in hyperimmunoglobulinemia G, the IgG4 subclass specifically increased as the autoantibodies, anti-nuclear antibodies and rheumatoid factors could be positive.
Hence, in a blood test for the present disease, these items namely gamma globulins, IgGs, IgG4, anti-nuclear antibodies (SS-A antibody and SS-B antibody) and rheumatoid factors, must be measured and thus the cost is very high, which is problematic. In addition, these test items are also increased or positive in other diseases so that the diagnostic specificity based upon measurement of the above items is poor. Further, even when the present disease is diagnosed in accordance with the above-described criteria, it is very difficult to distinguish from pancreatic cancer, and an unnecessary operation may be performed. And thus, a method for reliably distinguishing both diseases is desirable.
Each investigator has been searching for an autoantibody specific to AIP and thus far found activities of anti-blood lactoferrin (LF) antibody and anti-carbonic anhydrase II (CAII) antibody. Yet, the positive ratio of the antibodies in AIP is 73% and 53.8%, respectively, which lacks clinical sensitivity. Reliability and reproducibility of the method are poor. Therefore, these antibodies are inappropriate for diagnosis and differential diagnosis (Non-patent Literature References 1 and 2).
Furthermore, although monitoring the progress of an AIP treatment by a blood test is necessary for determining dosage and timing of administration, due to the same reasons as described above, the high testing cost is problematic.
Currently, diagnoses for FT1DM are carried out based on “Fulminant type 1 diabetes mellitus diagnostic criteria” presented by the research committee on fulminant diabetes mellitus of The Japan Diabetes Society in 2004. According to that, as a laboratory sample test, HbA1C, blood sugar level and C-peptide in urine or blood are measured. Further, as reference observations, it should be checked if autoantibodies such as GAD antibody and IA-2 antibody are negative and if blood pancreatic exocrine enzyme is increased.
Accordingly, with regard also to the present disease, a large number of items need to be tested, the cost for the diagnosis is high, and the test is non-specific, which is problematic.
Additionally, in many cases, the present disease develops into ketoacidosis within several days after the onset of the symptoms of hyperglycemia. Thus, without reliable diagnosis and prompt initiation of the treatment, the patient faces a life-threatening situation. Also, the disease often develops during pregnancy, which causes fetal death in most cases. Accordingly, it is desirable that the above-described test items be measured upon the onset of general diabetes mellitus to distinguish FT1DM from type 1 diabetes mellitus and type 2 diabetes mellitus. Yet, because no test marker for a good diagnosis to exclude FT1DM is available and the number of the test items is large, in reality, the differential diagnosis is not carried out.
Non-patent Literature 1: N. Engl. J. Med. 2001, 344:732-8
Non-patent Literature 2: J. Gastroenterol. 2001, 36:293-302